Mutations in at least eight genes affecting the repair of ultraviolet-induced DNA damage have been identified among patients with xeroderma pigmentosum. The proposed studies will compare the responses of cells from normals and from patients with these different forms of xeroderma pigmentosum to ultraviolet damage. The studies have five interrelated objectives: 1) To determine the relationship between DNA repair capacity and the cell cycles, by studying colony-forming ability following ultraviolet radiation in synchronized fibroblast cultures derived from patients with xeroderma pigmentosum. 2) To identify the portion of the UV spectrum (i.e., the action spectrum) responsible for the photochemical damage to which patients with xeroderma pigmentosum are susceptible. This will be accomplished by studying cell survival following irradiation with different ultraviolet sources. 3) To assess the possible interactions of different wavelengths of UV in the repair processes of cells from normal and xeroderma pigmentosum patients, by comparing the effects of combined and separate irradiations with different portions of the UV spectrum. 4) To assess the role of "inducible" (and presumably mutagenic) repair processes in cells of normal and xeroderma pigmentosum patients, by seeking to demonstrate an enhanced survival of ultraviolet-irradiated cells following the administrations of small "inducing" doses. 5) To continue the identification and characterization of new repair mutations in xeroderma pigmentosum patients, by determining repair synthesis rates, complementation groups, and ultraviolet sensitivity. The overall goal of these studies is to increase our understanding of the relationship between human DNA repair and environmentally-induced diseases of the skin and other organs.